Coin-tossing by Kinesin-1 Head and Tail Binding Collectively Drives Microtubule Patterns

Abstract

Intracellular microtubule-based transport depends on an essential plus-ended molecular motor, kinesin-1. The N-terminal ATP-dependent head driving motility and a C-terminal cargo interacting tail, both bind microtubules. Previously, the interplay of both domains were hypothesized to play a role in collective microtubule sliding patterns, but the mechanisms remained unclear. Here, we show that full-length Drosophila kinesin-1 generates striking spatiotemporal patterns in gliding assays including bending, looping, and oscillations as well as stop-and-go motion of filaments. In presence of the motor domain alone these patterns are absent, but with the tail only construct, microtubules bind passively, with the tail acting as a static anchor. An equimolar mixture of these two domain constructs reproduces these spatio-temporal patterns both in terms of increased bending with length and velocity distributions. Our results support a simple coin-toss model, where either head or tail bind microtubules with equal probability, leading to antagonistic interactions that drives emergent motility patterns and velocity distributions. Thus the kinesin tail plays an active mechanical role beyond regulation or cargo binding, modulating microtubule behavior through inter-domain competition.